There are many instances in which it is desirable to remove substances from fluids. Particularly in the case of biological fluids it is possible to treat certain pathological conditions by removing detrimental substances from the blood. For example, extracorporeal immunoadsorption has been implemented as a strategy for the removal of disease-associated molecules from the blood of patients. This methodology has the potential to provide therapeutic benefit in a variety of contexts including the treatment of rheumatoid arthritis, mysethenia gravis, systemic lupus erythematosus (SLE), poisonings, overdose, cancer, amyloidosis and AIDS. This approach can be very useful due to its potential for highly specific removal of a target substance. Also, this approach has the potential to be more cost effective than classical drug discovery and is often the only therapeutic option in medical emergencies or in the terminally ill.
Several of the pathological conditions for which extracorporeal immunoadsorption has potential for providing therapeutic benefit are autoimmune conditions. These conditions are characterized by an abnormal immune response directed against normal autologous (self) tissues. Autoimmune diseases afflict huge numbers of individuals throughout the world. Known autoimmune disorders include diabetes mellitus, multiple sclerosis, autoimmune uveitis, rheumatoid arthritis, Addison's disease, thyroiditis, atrophic gastritis, myasthenia gravis, idiopathic thrombocytopenic purpura, hemolytic anemia, SLE, primary biliary cirrhosis, Wegener's granulomatosis, polyarteritisnodosa, and inflammatory bowel disease.
In certain autoimmune diseases, specific elements of the immune system predominate in mediating the pathogenic process, while in other autoimmune diseases, all of the components of the immune system combine to produce disease. Often, the abnormal immune response involves the presence in a patient's blood of antibodies which are part of the inappropriate self-destructive immune response. Antibodies are considered to play the major causal roles in diseases such as SLE, myasthenia gravis and Graves' disease.
A number of strategies have been used or proposed to suppress autoimmune diseases, most notably drugs, such as cyclophosphamide, cyclosporin A, methotrexate, and azathioprine. Steroid compounds, such as prednisone and methylprednisolone, are also employed in many instances. These drugs have limited long term efficacy against both cell- and antibody-mediated autoimmune diseases. Use of such drugs is limited because of their toxic side effects which include "global" immunosuppression. Prolonged treatment with these drugs inhibits the normal protective immune response to pathogenic microorganisms, thereby increasing the risk of infections. A further drawback is that immune-mediated elimination of aberrant cells is impaired and there is, this, an increased risk that malignancies will develop in patients receiving prolonged global immunosuppression.
Specifically exemplified herein is a new and advantageous treatment for autoimmune conditions. One autoimmune condition which can be treated according to the subject invention is SLE. It is well known that antibodies to histones are associated with SLE. Histones have a high affinity for glomerular basement membrane, such that when deposited onto it, they mediate the subsequent binding of immune complexes that form nephritic lesions. Direct evidence has shown that histones and anti-histone antibodies are present in the glomerular immune deposits of lupus-prone mice, as well as, in the renal biopsy of patients with SLE. There is a great need for an efficient and safe means for removing anti-histone antibodies producing an immediate benefit to the patient, as well as a long term benefit by activating B-cells which can then be eliminated by cytotoxic therapy.
The ability to accomplish extracorporeal removal of certain components from bodily fluids without increased risks to the patient has been established. Extracorporeal devices, such as kidney dialysis machines, are known in the art and have been shown to be therapeutically effective in eliminating abnormally high concentrations of certain components of serum. U.S. Pat. No. 4,801,449 which issued to Balint, Jr. et al. discloses an immunoadsorbentmaterial comprising Protein A for removing IgG from biological fluids as a method for treating Kaposi's sarcoma. U.S. Pat. No. 5,122,112, which issued to Jones teaches a method for treating antigen-related disease by identifying the predominant antigen associated with the disease and then using an antigen-specific immunoadsorbent to remove the antigen from a patient's system.
There remains a need for improving the efficiency of methods for extracorporeal treatment of blood. There is also a need for methods of removing constituents from other fluids.